Adjuvant nivolumab (Opdivo) showed a long-term disease-free survival (DFS) for the treatment of patients with muscle-invasive urothelial carcinoma (MIUC) at a high risk of disease recurrence, according to data from the 5-year analysis of the phase 3 CheckMate 274 trial (NCT02632409) published in Annals of Oncology.1 Additional findings from an analysis of circulating tumor DNA (ctDNA) also revealed that ctDNA assessment could be used to identify patients at the highest risk of disease recurrence.
At a minimum follow-up of 59.6 months, the median disease-free survival (DFS) was 21.9 months (95% CI, 18.8-36.9) among patients who received adjuvant nivolumab (n = 253) compared with 11.0 months (95% CI, 8.3-16.6) with placebo (n = 356; HR, 0.74; 95% CI, 0.61-0.90). Patients with detectable ctDNA expression after radical surgery in the investigational arm (n = 54) experienced a median DFS of 52.1 months (95% CI, 19.4-not estimable [NE]) vs 5.0 months (95% CI, 2.8-6.5) among those with undetectable ctDNA (n = 54; HR, 0.30; 95% CI, 0.18-0.48). In patients included in the ctDNA analysis with detectable ctDNA, the HR for DFS for the nivolumab vs the placebo arm was 0.35 (95% CI, 0.18-0.66). In patients with undetectable ctDNA, the DFS HR for the nivolumab vs the placebo arm was 0.99 (95% CI, 0.51-1.93).
“There is an unmet need to identify patients who are at the highest risk of recurrence and to identify patients who may benefit most from nivolumab. Recent focus has shifted toward the role of ctDNA as a noninvasive biomarker of minimal residual disease, to potentially stratify patients at high risk for recurrence and to guide adjuvant therapy decisions,” Matthew Galsky, MD, deputy director of Mount Sinai Tisch Cancer Center, and director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Mount Sinai Tisch Cancer Center in New York, New York, and coauthors wrote. Galsky is also a professor of medicine, hematology, and medical oncology, as well as a professor of urology at Mount Sinai Tisch Cancer Center.
5-Year Efficacy and ctDNA Results From CheckMate 274
- At a minimum follow-up of 59.6 months, the median DFS was 21.9 months among patients who received adjuvant nivolumab vs 11.0 months with placebo (HR, 0.74; 95% CI, 0.61-0.90).
- Patients with detectable ctDNA expression after radical surgery in the investigational arm experienced a median DFS of 52.1 months vs 5.0 months in those with undetectable ctDNA (HR, 0.30; 95% CI, 0.18-0.48).
- In patients included in the ctDNA analysis with detectable ctDNA, the HR for DFS for the nivolumab vs the placebo arm was 0.35 (95% CI, 0.18-0.66).
In August 2021, the FDA approved adjuvant nivolumab for the treatment of patients with high-risk urothelial carcinoma.2 The regulatory decision was based on prior data from CheckMate 274.
What were the key design characteristics of CheckMate 274 and the ctDNA Analysis?
CheckMate 274 was a double-blind, multicenter trial that enrolled patients with high-risk MIUC following radical surgery.1 To be eligible for the study, patients needed to have undergone radical cystectomy or nephroureterectomy with curative intent within 120 days of random assignment and be disease-free per clinical and radiologic assessment. Patients also needed to have an ECOG performance status of 0 or 1 and available tumor tissue for biomarker evaluation.
Patients were randomly assigned 1:1 to receive nivolumab at 240 mg or a matched placebo, both given intravenously every 2 weeks for up to 1 year or until disease recurrence, unacceptable toxicity, or withdrawal. Stratification occurred based on PD-L1 expression level (≥ 1% vs < 1% or indeterminate), pathological nodal status (N+ vs N0/x with < 10 nodes removed vs N0 with ≥ 10 nodes removed), and prior neoadjuvant cisplatin-based chemotherapy use (yes vs no).
The primary end point was DFS. Secondary end points included overall survival (OS), disease-specific survival (DSS), and nonurothelial tract recurrence-free survival (NUTRFS). Distant metastasis-free survival (DMFS) represented an exploratory end point.
At baseline, the mean ages in the nivolumab and placebo groups were 65.3 years (range, 30-92) and 65.9 years (range, 42-88), respectively. Most patients in both arms had an ECOG performance status of 0 (63% vs 62%), had a tumor origin at the bladder (79% vs 79%), and were White (75% vs 76%).
What were the additional findings from the 5-year analysis?
Additional findings from the study revealed that the median OS in the investigational and placebo arms was 75.0 months (95% CI, 56.7-NE) and 50.1 months (95% CI, 38.0-72.1), respectively (HR, 0.83; 95% CI, 0.67-1.02). The study authors noted that the prespecified boundary for statistical significance was not crossed at the time of the analysis; OS follow-up is ongoing.
Adjuvant nivolumab also displayed a significant DSS benefit vs placebo (HR, 0.79; 95% CI, 0.62-1.00). The median NUTRFS values were 25.9 months (95% CI, 19.4-42.6) and 13.7 months (95% CI, 8.4-20.7), respectively. The median DMFS was 51.5 months (95% CI, 28.3-66.5) with nivolumab vs 25.9 months (95% CI, 16.6-48.6) with placebo (HR, 0.77; 95% CI, 0.62-0.96).
“At the time of the previous 3-year analysis, the most common treatment-related adverse events included pruritus, fatigue, and diarrhea,” Galsky and his coauthors wrote. “Patients remain off treatment at this time, with no new safety signals reported.”
References
- Galsky MD, Gschwend JE, Milowsky MI, et al. Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274. Ann Oncol. 2026;37(1):69-78. doi:10.1016/j.annonc.2025.09.139
- US Food and Drug Administration approves Opdivo (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed February 20, 2026. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-Carcinoma/default.aspx
